Cellular and Molecular Life Sciences CMLS

, Volume 57, Issue 13, pp 1964–1969

Polysialic acids: potential in improving the stability and pharmacokinetics of proteins and other therapeutics

  • G. Gregoriadis*
  • A. Fernandes**
  • M. Mital
  • B. McCormack

DOI: 10.1007/PL00000676

Cite this article as:
Gregoriadis*, G., Fernandes**, A., Mital, M. et al. CMLS, Cell. Mol. Life Sci. (2000) 57: 1964. doi:10.1007/PL00000676

Abstract.

Naturally occurring polymers of N-acetylneuraminic acid (polysialic acids) are biodegradable, highly hydrophilic and have no known receptors in the body. Following intravenous injection, polysialic acids exhibit long half-lives in the blood circulation and have therefore been proposed as carriers of short-lived drugs and small peptides. In addition, shorter-chain polysialic acids can be used as a means to increase the circulatory half-life of proteins and thus serve as an alternative to the nonbiodegradable monomethoxypoly(ethylene glycol). Recent work has shown that covalent coupling of a low molecular weight polysialic acid (colominic acid) to catalase and asparaginase leads to a considerable increase of enzyme stability in the presence of proteolytic enzymes or blood plasma. Comparative studies in vivo with polysialylated and intact asparaginase revealed that polysialylation significantly increases the half-life of the enzyme. The highly hydrophilic and innocuous nature of polysialic acids renders them suitable as a means to prolong the circulation of peptides and proteins.

Key words. Polysialic acids; colominic acid; catalase; asparaginase.

Copyright information

© Birkhäuser Verlag Basel, 2000

Authors and Affiliations

  • G. Gregoriadis*
    • 1
  • A. Fernandes**
    • 1
  • M. Mital
    • 1
  • B. McCormack
    • 1
  1. 1.Centre for Drug Delivery Research School of Pharmacy, University of London, 29–39 Brunswick Square, London WC1N 1AX (United Kingdom), Fax +44 171 7535822, e-mail: gregoriadis@cua.ulsop.ac.uk US